Triggered high-output pacing therapy

ABSTRACT

A device and method for delivering electrical stimulation to the heart in order to improve cardiac function in heart failure patients. The stimulation is delivered as high-output pacing in which the stimulation is excitatory and also of sufficient energy to augment myocardial contractility. The device may be configured to deliver high-output pacing upon detection of cardiac decompensation.

CROSS REFERENCE TO RELATED APPLICATIONS

This application claims the benefit of U.S. Provisional Application No.61/090,485, filed on Aug. 20, 2008, under 35 U.S.C. §119(e), which ishereby incorporated by reference in its entirety.

This application is related to U.S. patent application Ser. No.11/860,957 filed on Sep. 25, 2007, now U.S. Pat. No. 8,131,363, andassigned to Cardiac Pacemakers, Inc., the disclosure of which isincorporated by reference in its entirety.

FIELD OF THE INVENTION

This invention pertains to apparatus and methods for the treatment ofheart disease and to devices providing electrostimulation to the heartsuch as cardiac pacemakers.

BACKGROUND

Heart failure (HF) is a debilitating disease that refers to a clinicalsyndrome in which an abnormality of cardiac function causes a belownormal cardiac output that can fall below a level adequate to meet themetabolic demand of peripheral tissues. Heart failure can be due to avariety of etiologies with ischemic heart disease being the most common.Heart failure is usually treated with a drug regimen designed to augmentcardiac function and/or relieve congestive symptoms.

Electrostimulation of the ventricles can also be useful in treatingheart failure. It has been shown that some heart failure patients sufferfrom intraventricular and/or interventricular conduction defects (e.g.,bundle branch blocks) such that their cardiac outputs can be increasedby improving the synchronization of ventricular contractions withelectrical stimulation. In order to treat these problems, implantablecardiac devices have been developed that provide appropriately timedelectrical stimulation to one or more heart chambers in an attempt toimprove the coordination of atrial and/or ventricular contractions,termed cardiac resynchronization therapy (CRT). Ventricularresynchronization is useful in treating heart failure because, althoughnot directly inotropic, resynchronization can result in a morecoordinated contraction of the ventricles with improved pumpingefficiency and increased cardiac output. Currently, a most common formof CRT applies stimulation pulses to both ventricles, eithersimultaneously or separated by a specified biventricular offsetinterval, and after a specified atrio-ventricular delay interval withrespect to the detection of an intrinsic atrial contraction or deliveryof an atrial pace.

It has also been demonstrated that electrostimulatory pulses deliveredto the heart during its refractory period can augment myocardialcontractility. Applying contractility augmenting stimulation to theventricles can thus aid in the treatment of heart failure. Suchstimulation, sometimes referred to as cardiac contractility modulation(CCM), can be delivered during the refractory period after an intrinsiccontraction and hence is non-excitatory. Presumably, such stimulationincreases myocardial contractility by increasing intracellular calciumconcentration and/or eliciting release of neurotransmitters.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 illustrates the physical configuration of an exemplary pacingdevice.

FIG. 2 shows the components of an exemplary device.

FIG. 3 is a block diagram of the electronic circuitry of an exemplarydevice.

FIG. 4 illustrates a HOP mode.

FIG. 5 illustrates a HOP mode.

FIG. 6 illustrates an exemplary procedure for optimizing HOPstimulation.

FIG. 7 illustrates an exemplary algorithm for controlling entry and exitinto the HOP mode.

DETAILED DESCRIPTION

As noted above, CCM stimulation can be delivered in a non-excitatorymanner during the refractory period after an intrinsic contraction. Ithas been found that such non-excitatory CCM stimulation enhancescontractility in a generally consistent manner such that contractilityis enhanced for every beat and is relatively insensitive to variationsin stimulation parameters such as stimulation pulse duration, andstimulation timing. Contractility augmenting stimulation can also beapplied in an excitatory manner, however, referred to herein ashigh-output pacing (HOP). In one form of HOP, the stimulation isdelivered in the same manner as conventional pacing using a bradycardiapacing mode using stimulation pulses with a higher stimulation energy.For example, a stimulation pulse for high-output pacing may be abiphasic (or multiphasic) waveform having a peak-to-peak voltageamplitude of + or −5-8 volts and a pulse duration of 50-70 milliseconds.In another form of HOP, similar stimulation pulses are delivered in therefractory period following a conventional ventricular pacing pulse.Unlike as is the case for non-excitatory CCM, it has been found that HOPis sensitive to stimulation parameters such as the stimulation site,stimulation pulse duration, and stimulation timing. Unless thoseparameters are optimized, contractility enhancement by HOP isinconsistent from beat to beat. This disclosure describes methods anddevices for delivering HOP in which stimulation parameters are optimizedin accordance with a measured hemodynamic response.

An exemplary device for delivering HOP stimulation may be a device withthe capability for also delivering bradycardia pacing, CRT,cardioversion/defibrillation shocks, and/or neural stimulation. Thedevice is equipped with multiple stimulation electrodes that can beplaced at different sites in the ventricle and/or atrium by means ofunipolar or multipolar leads. The stimulation electrodes are switchablyconnected to pulse generation circuitry for delivering stimulationpulses to selected stimulation sites. The HOP stimulation pulses can bedelivered from one or multiple stimulation electrodes, eithersimultaneously or with timing offsets between them. In order to optimizethe stimulation parameters, the device is configured to measure thehemodynamic response while the HOP is delivered from single or multiplesites and to adjust the stimulation parameters in a manner that resultsin the most improvement. In order to measure hemodynamic response, thedevice is equipped with the capability of measuring one or morephysiological variables that are reflective of myocardial contractility.Examples of such variables include heart sound amplitudes (e.g., theamplitude of the sound mitral valve closure during systole), systolicblood pressure, or cardiac stroke volume (e.g., as measured by atransthoracic impedance sensor). The stimulation site or sites, theamplitude of stimulation, the polarity (only positive, only negative,biphasic, unbalanced waveforms), the stimulation pulse duration, thenumber of pulses and the timing of the stimulation pulses may then beadjusted in order to maximally augment contractility. The stimulationparameter optimization procedure involves delivering HOP with particularstimulation parameters and measuring the hemodynamic response as thestimulation parameters are changed in some prescribed manner. Thestimulation parameter optimization procedure may be performed atperiodic intervals, upon command received via telemetry, or in responseto one or more measured parameters that indicate the patient's clinicalstatus may have changed. Examples of the latter could include thehemodynamic response parameters used in the stimulation parameteroptimization procedure or other parameters such as heart rate, heartrate variability, or other measures of autonomic tone. The device may beconfigured to deliver HOP either continuously or intermittently. In thelatter case, the device enters an HOP mode according to specified entryand exit conditions where the specified entry and exit conditions may belapsed time intervals, sensed parameter values, or combinations thereof.

1. Exemplary Cardiac Device

FIG. 1 shows an implantable cardiac pacing device 100 for deliveringpacing therapy including HOP. Implantable pacing devices are typicallyplaced subcutaneously or submuscularly in a patient's chest with leadsthreaded intravenously into the heart to connect the device toelectrodes disposed within a heart chamber that are used for sensingand/or pacing of the chamber. Electrodes may also be positioned on theepicardium by various means. A programmable electronic controller causesthe pacing pulses to be output in response to lapsed time intervalsand/or sensed electrical activity (i.e., intrinsic heart beats not as aresult of a pacing pulse). The device senses intrinsic cardiacelectrical activity through one or more sensing channels, each of whichincorporates one or more of the electrodes. In order to excitemyocardial tissue in the absence of an intrinsic beat, pacing pulseswith energy above a certain threshold are delivered to one or morepacing sites through one or more pacing channels, each of whichincorporates one or more of the electrodes. FIG. 1 shows the exemplarydevice having two leads 200 and 300, each of which is a multi-polar(i.e., multi-electrode) lead having electrodes 201-203 and 301-303,respectively. The electrodes 201-203 are disposed in the right ventriclein order to stimulate or sense right ventricular or septal regions,while the electrodes 301-303 are disposed in the coronary sinus in orderto stimulate or sense regions of the left ventricle. Other embodimentsmay use any number of electrodes in the form of unipolar and/ormulti-polar leads in order to sense or stimulate different myocardialsites. Once the device and leads are implanted, the pacing and/orsensing channels of the device may be configured with selected ones ofthe multiple electrodes in order to selectively stimulate or sense aparticular myocardial site(s). As described below, the pacing channelsmay be used to deliver conventional bradycardia pacing, CRT, or HOPtherapy.

FIG. 2 shows the components of the implantable device 100 in moredetail. The implantable device 100 includes a hermetically sealedhousing 130 that is placed subcutaneously or submuscularly in apatient's chest. The housing 130 may be formed from a conductive metal,such as titanium, and may serve as an electrode for deliveringelectrical stimulation or sensing in a unipolar configuration. A header140, which may be formed of an insulating material, is mounted on thehousing 130 for receiving leads 200 and 300 which may be thenelectrically connected to pulse generation circuitry and/or sensingcircuitry. Contained within the housing 130 is the electronic circuitry132 for providing the functionality to the device as described hereinwhich may include a power supply, sensing circuitry, pulse generationcircuitry, a programmable electronic controller for controlling theoperation of the device, and a telemetry transceiver capable ofcommunicating with an external programmer or a remote monitoring device.

FIG. 3 shows a system diagram of the electronic circuitry 132. A battery22 supplies power to the circuitry. The controller 10 controls theoverall operation of the device in accordance with programmedinstructions and/or circuit configurations. The controller may beimplemented as a microprocessor-based controller and include amicroprocessor and memory for data and program storage, implemented withdedicated hardware components such as ASICs (e.g., finite statemachines), or implemented as a combination thereof. The controller alsoincludes timing circuitry such as external clocks for implementingtimers used to measure lapsed intervals and schedule events. As the termis used herein, the programming of the controller refers to either codeexecuted by a microprocessor or to specific configurations of hardwarecomponents for performing particular functions. Interfaced to thecontroller are sensing circuitry 30 and pulse generation circuitry 20 bywhich the controller interprets sensing signals and controls thedelivery of paces and/or HOP stimulation pulses in accordance with apacing mode. The controller is capable of operating the device in anumber of programmed pacing modes which define how pulses are output inresponse to sensed events and expiration of time intervals. Thecontroller also implements timers derived from external clock signals inorder to keep track of time and implement real-time operations such asscheduled entry into a HOP mode.

The sensing circuitry 30 receives atrial and/or ventricular electrogramsignals from sensing electrodes and includes sensing amplifiers,analog-to-digital converters for digitizing sensing signal inputs fromthe sensing amplifiers, and registers that can be written to foradjusting the gain and threshold values of the sensing amplifiers. Thesensing circuitry of the pacemaker detects a chamber sense, either anatrial sense or ventricular sense, when an electrogram signal (i.e., avoltage sensed by an electrode representing cardiac electrical activity)generated by a particular channel exceeds a specified detectionthreshold. Pacing algorithms used in particular pacing modes employ suchsenses to trigger or inhibit pacing, and the intrinsic atrial and/orventricular rates can be detected by measuring the time intervalsbetween atrial and ventricular senses, respectively. The pulsegeneration circuitry 20 delivers conventional pacing and/or HOP pulsesto pacing electrodes disposed in the heart and includes capacitivedischarge or current source pulse generators, registers for controllingthe pulse generators, and registers for adjusting parameters such aspulse energy (e.g., pulse amplitude and width). The pulse generationcircuitry may also include a shocking pulse generator for delivering adefibrillation/cardioversion shock via a shock electrode upon detectionof a tachyarrhythmia.

A telemetry transceiver 80 is interfaced to the controller which enablesthe controller to communicate with an external device such as anexternal programmer and/or a remote monitoring unit. An externalprogrammer is a computerized device with an associated display and inputmeans that can interrogate the pacemaker and receive stored data as wellas directly adjust the operating parameters of the pacemaker. Theexternal device may also be a remote monitoring unit that may beinterfaced to a patient management network enabling the implantabledevice to transmit data and alarm messages to clinical personnel overthe network as well as be programmed remotely. The network connectionbetween the external device and the patient management network may beimplemented by, for example, an internet connection, over a phone line,or via a cellular wireless link. A switch 24 is also shown as interfacedto the controller in this embodiment to allow the patient to signalcertain conditions or events to the implantable device. In differentembodiments, the switch 24 may be actuated magnetically, tactilely, orvia telemetry such as by a hand-held communicator. The controller may beprogrammed to use actuation of the switch 24 to as an entry and/or exitcondition for entering a HOP mode.

A pacing channel is made up of a pulse generator connected to anelectrode, while a sensing channel is made up of a sense amplifierconnected to an electrode. Shown in the figure are electrodes 40 ₁through 40 _(N) where N is some integer. The electrodes may be on thesame or different leads and are electrically connected to a MOS switchmatrix 70. The switch matrix 70 is controlled by the controller and isused to switch selected electrodes to the input of a sense amplifier orto the output of a pulse generator in order to configure a sensing orpacing channel, respectively. The device may be equipped with any numberof pulse generators, amplifiers, and electrodes that may be combinedarbitrarily to form sensing or pacing channels. The device is thereforecapable of delivering single-site or multiple site ventricular pacingand/or HOP stimulation. The switch matrix 70 also allows selected onesof the available implanted electrodes to be incorporated into sensingand/or pacing channels in either unipolar or bipolar configurations. Abipolar sensing or pacing configuration refers to the sensing of apotential or output of a pacing pulse between two closely spacedelectrodes, where the two electrodes are usually on the same lead (e.g.,a ring and tip electrode of a bipolar lead or two selected electrodes ofa multi-polar lead). A unipolar sensing or pacing configuration is wherethe potential sensed or the pacing pulse output by an electrode isreferenced to the conductive device housing or another distantelectrode.

The device may also include one or more physiological sensing modalities25 for use in controlling the pacing rate, optimization of HOPstimulation parameters, and/or the initiation/cessation of the HOP mode.One such sensing modality is an accelerometer that enables thecontroller to detect changes in the patient's physical activity, detectpatient posture (i.e., using a multi-axis accelerometer), and/or detectheart sounds. A dedicated acoustic sensor that may be of various typesmay also be used to detect heart sounds. An impedance sensor may beconfigured with electrodes for measuring minute ventilation for use inrate adaptive pacing and/or for measuring cardiac stroke volume orcardiac output. The device may also include a pressure sensor that maybe used, for example, to measure pressure in the pulmonary artery orelsewhere.

2. Optimization of HOP Stimulation Parameters

As described above, HOP therapy for augmenting myocardial contractilityrequires optimization of stimulation parameters for consistent results.The controller of the implantable pacing device may be programmed toperform an optimization procedure to select optimal stimulationparameters for delivering HOP. In such a procedure, the controllercycles through selected sets of different stimulation parameters whiledelivering HOP and measures the hemodynamic response to each stimulationparameter set using one or more of the device's sensing modalities. Onestimulation parameter that may be included in the parameter set is thestimulation site (or sites) to which HOP stimulation is delivered. Thedevice may be implanted with multiple leads and/or multipolar leads thatallow disposition of stimulation electrodes at a plurality of differentendocardial or epicardial sites. One site that has been found to oftenbe responsive is the anterior and posterior AV groove at the level ofthe valve. The controller utilizes the switch matrix to select differentstimulation electrodes for delivering HOP to different sites during theoptimization procedure. Other stimulation parameters that can beincluded in a parameter set relate to the stimulation pulse waveform andthe timing for delivering the pulses. As noted above, HOP can bedelivered as high-energy excitatory pulses in accordance with abradycardia pacing mode, referred to herein as Mode 2. The HOPstimulation pulse is of longer duration than a conventional pacingpulse, and the duration of the pulse PD is a parameter that affects thecontractility response. HOP can also be delivered during the refractoryperiod following a ventricular pace, referred to herein as Mode 1. Thestimulation pulse waveform for Mode 1 may be similar to that used forMode 2, and the pulse duration PD may be similarly adjusted for maximalcontractility response. Another stimulation parameter for Mode 1 is thedelay DLY between the ventricular pacing pulse and the HOP stimulationpulse delivered during the refractory period. FIGS. 4 and 5 illustratethe timing of the stimulation pulses for Modes 1 and 2, respectively, asdelivered in an atrial tracking mode in relation to an ECG. FIG. 4 showsa HOP stimulation pulse of duration PD that follows a ventricular pacingpulse V_(p) by a delay DLY. FIG. 5 shows an excitatory HOP stimulationpulse of duration PD. For both modes, the AV delay following an atrialpace A_(p) (or an atrial sense) for delivering the ventricular pacingpulse or the excitatory HOP pulse is another stimulation parameter thatmay be optimized. Another parameter that may be optimally adjusted forboth modes is the type (e.g., number of phases, amplitude) of the HOPstimulation waveform.

FIG. 6 illustrates an exemplary optimization procedure that may beexecuted by the device controller. Such an optimization procedure may beexecuted at periodic intervals, upon command, in response to sensedparameters or events, or whenever the HOP mode is entered if the HOP isdelivered intermittently. At step S1, a particular parameter set isselected from a list of parameter sets to be tested, where the parameterset may specify the HOP mode (e.g., Mode 1 or Mode 2), the stimulationsite or sites, the stimulation pulse duration PD, the delay DLY if Mode1 is selected, and/or the AV delay for delivering a ventricular pace orHOP stimulation pulse in an atrial tracking pacing mode. At step S2, HOPis delivered for a specified number of beats using the selectedparameter set while the hemodynamic response is concurrently monitoredat step S3. As discussed earlier, in order to measure the hemodynamicresponse, the device is equipped with the capability of measuring one ormore physiological variables that are reflective of myocardialcontractility. Examples of such variables include heart sound amplitudes(e.g., the amplitude of the sound mitral valve closure during systole),systolic blood pressure, or cardiac stroke volume (e.g., as measured bya transthoracic impedance sensor). At step S4, hemodynamic response isevaluated (e.g., by comparing the physiological variables to specifiedthreshold values over the specified number of beats), and the selectedparameter set and hemodynamic response is saved if the hemodynamicresponse is deemed adequate. Adequacy of the hemodynamic response maydepend upon both the magnitude and the consistency of the hemodynamicresponse over the specified number of beats. At step S5, the procedureloops back to step S1 if there are still parameter sets in the list tobe tested. Otherwise, at step S6, it is determined whether any of theparameter sets in the list have produced an adequate hemodynamicresponse. If not, the controller discontinues (or does not initiate) HOPat step S7. Otherwise, the controller delivers HOP using the savedparameter set that produces the best hemodynamic response at step S8.

3. Delivery of Intermittent High-Output Pacing Stimulation

As described above, HOP stimulation of the heart can be used to improvesystolic function in HF patients by increasing myocardial contractility.Chronic HOP stimulation of the heart, however, could overstress theheart in certain HF patients and be hazardous. Accordingly, in suchpatient, HOP stimulation should be delivered on an intermittent basis.The pacing device controller may be configured to deliver intermittentHOP stimulation by switching from a normal operating mode to a HOPstimulation mode. In the normal operating mode, the device may deliverno therapy at all or may be configured to delivery therapies such asbradycardia pacing, cardiac resynchronization pacing, and/or shocks oranti-tachycardia pacing in response to detection of tachyarrhythmias.

The device may be configured to use one or more entry and/or exitconditions in controlling entry and/or exit into the HOP mode. An entryor exit condition could be, for example, a lapsed time interval (e.g.,specified time(s) of the day), actuation of a switch by the patient(e.g., a magnetically or tactilely actuated switch interfaced to thedevice controller), a command received via telemetry, detection ornon-detection of a condition such as upright posture, or a measuredvariable being within or out of a specified range. Examples of suchmeasured variables include heart rate, activity level, minuteventilation, cardiac output, heart sounds, and blood pressure. Entryand/or exit conditions may also be composite conditions where aplurality of entry and/or exit conditions are logically ORed or ANDedtogether to determine whether a composite entry or entry condition issatisfied. FIG. 7 illustrates an exemplary algorithm executable by thedevice controller for controlling entry and exit into the HOP mode. Asshown in the figure, the controller of the device is programmed totransition through a number of different states, designated as A1through A4. At state A1, the device operates in its normal operatingmode. At state A2, while continuing to operate in state A1, the devicedetermines whether it should switch to the HOP mode by testing for oneor more particular entry conditions. If an entry condition is satisfied,the device switches to the HOP mode at step A3. Examples of entryconditions that must be satisfied before the switch to the HOP modeinclude a measured exertion level being within a specified entry range(where exertion level may be measured by, e.g., heart rate, activitylevel, or minute ventilation), non-detection of cardiac arrhythmias,non-detection of cardiac ischemia, receipt of a telemetry command, andactuation by the patient of a magnetically or tactilely actuated switchincorporated into the device that allows switching to the HOP mode.While executing in the HOP mode, the device monitors for one or moreexit conditions which cause the device to revert to the normal operatingmode. Such exit conditions could be the same or different from the entryconditions that must be satisfied before entering the HOP mode. Examplesof exit conditions include a measured exertion level being outside aspecified permissible range, a measured heart rate being outside aspecified permissible range, presence of a cardiac arrhythmia, presenceof cardiac ischemia, receipt of a telemetry command, and actuation bythe patient of a magnetically or tactilely actuated switch incorporatedinto the device by the patient to stop delivery of HOP stimulation. Ifan exit condition occurs, the device returns to the normal operatingmode at state A1.

4. Delivery of High-Output Pacing Stimulation in Response to Detectionof Decompensation

Cardiac failure refers to a condition in which the heart fails to pumpenough blood to satisfy the needs of the body, usually due to somedamage to the heart itself, such as from a myocardial infarction orheart attack. When heart failure occurs acutely, autonomic circulatoryreflexes are activated that both increase the contractility of the heartand constrict the vasculature as the body tries to defend against thedrop in blood pressure. Venous constriction, along with the reduction inthe heart's ability to pump blood out of the venous and pulmonarysystems (so-called backward failure), causes an increase in thediastolic filling pressure of the ventricles. This increase in preload(i.e., the degree to which the ventricles are stretched by the volume ofblood in the ventricles at the end of diastole) causes an increase instroke volume during systole, a phenomena known as the Frank-Starlingprinciple. If the heart failure is not too severe, this compensation isenough to sustain the patient at a reduced activity level. When moderateheart failure persists, other compensatory mechanisms come into playthat characterize the chronic stage of heart failure. The most importantof these is the depressing effect of a low cardiac output on renalfunction. The increased fluid retention by the kidneys then results inan increased blood volume and further increased venous return to theheart. A state of compensated heart failure results when the factorsthat cause increased diastolic filling pressure are able to maintaincardiac output at a normal level even while the pumping ability of theheart is compromised.

Compensated heart failure, however, is a precarious state. If cardiacfunction worsens or increased cardiac output is required due toincreased activity or illness, the compensation may not be able tomaintain cardiac output at a level sufficient to maintain normal renalfunction. Fluid then continues to be retained, causing the progressiveperipheral and pulmonary edema that characterizes overt congestive heartfailure. Diastolic filling pressure becomes further elevated whichcauses the heart to become so dilated and edematous that its pumpingfunction deteriorates even more. This condition, in which the heartfailure continues to worsen, is decompensated heart failure. It can bedetected clinically, principally from the resulting pulmonary congestionand dyspnea, and all clinicians know that it can lead to rapid deathunless appropriate therapy is instituted.

Decompensated heart failure is primarily a result of the heart failingto pump sufficient blood for the kidneys to function adequately andmaintain fluid balance. When cardiac output falls, renal perfusiondecreases which results in reduced glomerular filtration and reducedurine output. The decreased blood flow to the kidneys also activates therennin-angiotensin system which further reduces renal perfusion andpromotes the reabsorption of water and salt from the renal tubules. Inthe latter stages of this process, angiotensin stimulates secretion ofaldosterone which causes a further increase in the reabsorption ofsodium. The increase in sodium reabsorption raises the osmolarity of theblood which then elicits secretion of vasopressin and increased tubularreabsorption of water. Excess fluid retention brought about by renalcompensation for heart failure has a diluting effect on the blood, thusdecreasing the patient's hematocrit, where the hematocrit is defined asthe percentage of red blood cells in the blood.

By monitoring the fluid status of a patient (e.g., hematocrit and/orplasma osmolarity), the physiologic changes leading to decompensatedheart failure may be detected at an early stage before clinical symptomsbecome apparent. An implantable device for monitoring a patient's fluidstatus in order to detect cardiac decompensation is described in U.S.Pat. No. 7,356,366, assigned to Cardiac Pacemakers, Inc. and herebyincorporated by reference. Accordingly, the implantable device fordelivering HOP therapy as described herein may be similarly equippedwith sensor(s) for measuring the patient's hematocrit, plasmaosmolarity, or other parameters indicative of fluid status. The devicethen compares the fluid status parameter to a threshold value and, if adeviation from the threshold value to a predetermined extent is found,decompensation is detected. The device then uses such detection ofdecompensation as an entry condition for initiating HOP therapy in orderto improve systolic function. The device may also be configured todetect other variables that are correlated with cardiac decompensationto trigger HOP therapy such as an augmented S3 heart sound as detectedwith an accelerometer, changes in heart rate including increasingsympathetic tone as detected from heart rate variability, changes in thepatient's weight as communicated to the device via telemetry, detectionof pulmonary edema or changes in breathing patterns via an impedancesensor, an increase in pulmonary artery pressure (or other bloodpressure changes) as detected by an indwelling pressure sensor connectedto the device, or changes in cardiac stroke volume as detected by animpedance sensor. Any these variables may be used alone or incombination as entry conditions for triggering HOP therapy in order totreat decompensation. Alternatively, direct sympathetic neuralstimulation (stellate ganglion, etc) may be performed upon detection ofthe decompensation event or such sympathetic nerve stimulation may becombined with HOP for enhanced effect. Methods and devices for suchneural stimulation are described in co-pending U.S. patent applicationSer. No. 11/539,301, now issued as U.S. Pat. No. 7,664,548, assigned toCardiac Pacemakers, Inc. and hereby incorporated by reference. Onceinitiated, HOP therapy for treating decompensation may be terminatedafter a programmed exit condition (e.g., lapsing of predetermined timeinterval, detection of an arrhythmia, or receipt of command) occurs asdescribed above.

5. Delivery of Intermittent High-Output Pacing Stimulation Based UponCircadian Patterns

As described above, HOP therapy may be initiated upon detection of anentry condition that indicates a decrease in myocardial contractility.Myocardial contractility may be monitored, for example, by measuring theamplitude of heart sounds via an accelerometer, employing a lead-basedcontractility measure (e.g., a fiber-optic lead), measuring changes insystolic blood pressure with an indwelling pressure monitor, ordetecting changes in cardiac stroke volume or cardiac output via animpedance measurement. The HOP therapy then serves to counteract thedetected decrease in myocardial contractility to at least partiallyrestore normal systolic function. Another way that HOP therapy may beemployed for beneficial effect, however, is to condition the myocardiumeven when systolic function is normal. HOP therapy delivered in thismanner may mimic the effects of exercise and strengthen the heartmuscle. Accordingly the device may be programmed to deliver HOP therapywhen it is most convenient for the patient and/or likely to have themost beneficial effect. One way to deliver HOP therapy in this situationis based upon the patient's circadian patterns. The device may beconfigured to detect such circadian patterns based upon, for example,the actual time of day as detected by the device's internal timer,indications of posture change as detected by a multi-axis accelerometer,changes in heart rate or breathing patterns, and changes in autonomicbalance as detected from heart rate variability. The device may then beprogrammed to estimate when the patient is sleeping and use the estimateas an entry condition for initiating HOP therapy. For example, thedevice may be programmed to deliver HOP therapy either continuously orfor short time periods within a night and terminate the HOP upondetection of an arrhythmia (or pro-arrhythmic condition) or detection ofsleep disordered breathing such as apnea.

The invention has been described in conjunction with the foregoingspecific embodiments. It should be appreciated that those embodimentsmay also be combined in any manner considered to be advantageous. Also,many alternatives, variations, and modifications will be apparent tothose of ordinary skill in the art. Other such alternatives, variations,and modifications are intended to fall within the scope of the followingappended claims.

What is claimed is:
 1. A cardiac rhythm management device, comprising:pulse generation circuitry for delivering electrical stimulation to oneor more electrodes; a switching matrix for connecting the pulsegeneration circuitry to one or more of a plurality of availableelectrodes disposed at a plurality of stimulation sites; a hemodynamicresponse sensor for sensing a physiological variable reflective ofmyocardial contractility; a controller programmed to, in a normal mode,deliver pacing pulses to a selected stimulation site using a bradycardiapacing mode; wherein the controller is programmed to, in a high-outputpacing (HOP) mode, deliver pacing pulses to an optimal HOP stimulationsite using a bradycardia pacing mode with a pacing pulse energy greaterthan in the normal mode; wherein the controller is programmed to cyclethrough a plurality of different stimulation sites by operating theswitch matrix to connect the pulse generator to different ones of theavailable electrodes in order to deliver HOP stimulation to thedifferent stimulation sites, compare the hemodynamic response sensoroutputs of each of the different stimulation sites white HOP stimulationis delivered thereto, and select the optimal HOP stimulation site basedupon the comparison; sensing circuitry for detecting cardiacdecompensation; wherein the controller is programmed to operate in thenormal mode and to intermittently enter and exit the HOP mode inaccordance with specified entry and exit conditions; and, wherein thedevice is programmed to use detection of cardiac decompensation as anentry condition for triggering delivery of HOP stimulation in the HOPmode.
 2. The device of claim 1 wherein the sensing circuitry fordetecting cardiac decompensation includes a sensor for measuring apatient's plasma osmolarity.
 3. The device of claim 1 wherein thesensing circuitry for detecting cardiac decompensation includes a sensorfor measuring a patient's hematocrit.
 4. The device of claim 1 whereinthe sensing circuitry for detecting cardiac decompensation includes anaccelerometer for detecting heart sounds.
 5. The device of claim 1wherein the sensing circuitry for detecting cardiac decompensationincludes an impedance sensor for detecting pulmonary edema or changes inbreathing patterns.
 6. The device of claim 1 wherein the sensingcircuitry for detecting cardiac decompensation includes one or moresensors for measuring a physiological variable related to myocardialcontractility.
 7. The device of claim 1 wherein the sensing circuitryfor detecting cardiac decompensation includes a sense amplifier forincorporation into a sensing channel for detecting heart rate and fordetecting increasing sympathetic tone as derived from heart ratevariability.
 8. The device of claim 1 wherein the sensing circuitry fordetecting cardiac decompensation includes a transceiver for receivingchanges in a patient's weight as communicated to the device viatelemetry.
 9. The device of claim 1 wherein the sensing circuitry fordetecting cardiac decompensation includes an indwelling pressure sensorconnected to the device for detecting an increase in pulmonary arterypressure or other blood pressure changes.
 10. The device of claim 1wherein the sensing circuitry for detecting cardiac decompensationincludes an impedance sensor for detecting changes in cardiac output.11. The device of claim 1 wherein the hemodynamic response sensor isselected from a heart sound sensor, an accelerometer, a pressure sensor,or a transthoracic impedance sensor.
 12. A method, comprising:configuring a cardiac device to deliver stimulation to one or moremyocardial stimulation sites through one or more stimulation channels byconnecting pulse generation circuitry to one or more of a plurality ofavailable electrodes; configuring the device to sense a physiologicalvariable reflective of myocardial contractility and detect cardiacdecompensation; programming a controller of the device to, in a normalmode, deliver pacing pulses to a selected stimulation site using abradycardia pacing mode and, in a high-output pacing (HOP) mode, deliverpacing pulses to an optimal HOP stimulation site using a bradycardiapacing mode with a pacing pulse energy greater than in the normal mode;programming the controller to cycle through a plurality of differentstimulation sites by operating the switch matrix to connect the pulsegenerator to different ones of the available electrodes in order todeliver HOP stimulation to the different stimulation sites, to comparethe hemodynamic response sensor outputs of each of the differentstimulation sites while HOP stimulation is delivered thereto, and toselect the optimal HOP stimulation site based upon the comparison;programming the controller to operate in the normal mode and tointermittently enter and exit the HOP mode in accordance with specifiedentry and exit conditions; and, programming the controller to usedetection of cardiac decompensation as an entry condition for triggeringdelivery of HOP stimulation in the HOP mode.
 13. The method of claim 12further comprising configuring the device to detect cardiacdecompensation by measuring a patient's plasma osmolarity.
 14. Themethod of claim 12 further comprising configuring the device to detectcardiac decompensation by measuring a patient's hematocrit.
 15. Themethod of claim 12 further comprising configuring the device to detectcardiac decompensation by using an accelerometer for detecting heartsounds.
 16. The method of claim 12 further comprising configuring thedevice to detect cardiac decompensation by using an impedance sensor fordetecting pulmonary edema or changes in breathing patterns.
 17. Themethod of claim 12 further comprising configuring the device to detectcardiac decompensation by using an indwelling pressure sensor connectedto the device for detecting an increase in pulmonary artery pressure orother blood pressure changes.
 18. The method of claim 12 wherein thesensed physiological variable sensor is selected from heart sounds,blood pressure, or cardiac stroke volume.